Rare and geographically restricted species may be vulnerable to genetic effects from inbreeding depression in small populations or from genetic swamping through hybridization with common species, but a third possibility is that selective gene flow can restore fitness (genetic rescue). Climate-sensitive pikas (Ochotona spp.) of the Qinghai–Tibetan Plateau (QHTP) and its vicinity have been reduced to residual populations through the movement of climatic zones during the Pleistocene and recent anthropogenic disturbance, while the plateau pika (O. curzoniae) remains common. Population-level whole-genome sequencing (n = 142) of six closely related species in the subgenus Ochotona revealed several phases of ancient introgression, lineage replacement, and bidirectional introgression. The strength of gene flow was greatest from the dominant O. curzoniae to ecologically distinct species in areas peripheral to the QHTP. Genetic analyses were consistent with environmental reconstructions of past population movements. Recurrent periods of introgression throughout the Pleistocene revealed an increase in genetic variation at first but subsequent loss of genetic variation in later phases. Enhanced dispersion of introgressed genomic regions apparently contributed to demographic recovery in three peripheral species that underwent range shifts following climate oscillations on the QHTP, although it failed to drive recovery of northeastern O. dauurica and geographically isolated O. sikimaria. Our findings highlight differences in timescale and environmental background to determine the consequence of hybridization and the unique role of the QHTP in conserving key evolutionary processes of sky island species.
Aim The mechanisms by which global biodiversity hotspots harbour and conserve high genetic and morphological diversity of endemic species remain unexplored. Relic species of ochotonids in the genus Ochotona are confined to alpine habitats and highly sensitive to environmental changes. We studied the genomic and ecological mechanisms underlying the divergence and adaptive evolution of the Moupin pika (O. thibetana) and its closely related species to infer its diversification, adaptive evolution and demographic history in response to historical and recent environmental changes. Location Hengduan Mountain Region, China. Methods We integrated morphological, genomic and ecological data to interpret the phylogeographic structure, adaptive evolution, demographic history and range shift of O. thibetana. Phylogenetic reconstruction was based on Cytochrome b (CYTB), the mitochondrial genome and single‐copy orthologues of the whole genome. Gene flow among extant lineages, as well as from extinct species, was inferred by multiple algorithms. Demographic history was inferred using the pairwise sequential Markovian coalescent and high‐resolution analysis of linkage disequilibrium. We also predicted the range shift of this species by using ecological niche modelling. Results Phylogenetic reconstruction revealed an unusual mitochondrial lineage of O. thibetana from the western Sichuan Basin, which was named O. qionglaiensis in previous studies. Extensive gene flow was detected among genetic lineages of O. thibetana, which has distinct phenotypic variation in hair thickness and colouration, as well as notable morphological differentiation in external and craniodental measurements. Multiple members of the keratin gene family were identified as introgressed loci from some ancient species to O. thibetana. The Moupin pika underwent dramatic population shrinkage in the late Quaternary, with a clear trend of population growth in approximately the last 70 generations. The potential distribution range of O. thibetana showed a clear trend of expansion in the future. Main conclusions The unusual mitochondrial phylogenetic pattern of O. thibetana resulted from “extended ghost introgression,” a new evolutionary model proposed in the present study, and thus rejected the validity of O. qionglaiensis as an independent species. Ancient introgression of keratin genes likely underlies the prominent coat phenotypic variation among genetic lineages. Clear population growth and range expansion of the Moupin pika in recent generations probably benefitted from recent global warming and vegetation recovery, which not only contributed to the conservation of large mammals but was also beneficial to small mammals endemic to alpine habitats.
About 80% of hepatocellular carcinoma (HCC) patients are in advanced stages and ineligible for curative surgery. Palliative treatments just maintained limited survival, thus an effective downstaging therapy is badly needed. Here we report an initially unresectable patient who underwent radical hepatectomy after successful downstaging with selective internal radiation therapy (SIRT). A 34‐year‐old man was diagnosed with China Liver Cancer Staging (CNLC) IIIa HCC. Due to insufficient future liver remnant and vascular involvement, the patient was suggested to be unresectable. SIRT with yttrium‐90 resin microspheres was given. At three months post‐SIRT, a complete response was achieved. The tumor was downstaged to CNLC Ia stage. The patient underwent anatomical hepatectomy 5 months after SIRT. Histopathological examination of the resected specimen showed 4% viable tumor cells inside a necrotic mass. To our knowledge, this is the first case who underwent SIRT with yttrium‐90 resin microspheres in China mainland. The success of the downstaging in this case renders a possible cure to be achieved in an initially unresectable patient. In addition, the nearly complete tumor necrosis in the resected specimen indicates a good prognosis post‐surgery. This is the first case who underwent SIRT with yttrium‐90 resin microspheres in China mainland. SIRT followed by anatomical hepatectomy is a potentially curative strategy for unresectable HCC, which deserves a confirmative trial in the future.
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